Citations

ABSTRACT Background and Purpose Corticospinal tract (CST) integrity is an imaging biomarker for predicting upper extremity motor recovery, but data are limited in acute ischemic stroke patients. Our study aimed to assess the impact of CST disruption on upper extremity motor recovery after acute ischemic stroke. Methods We enrolled patients with upper extremity motor deficits within 7 days of stroke onset. Patients’ clinical status was assessed for the upper extremity Fugl–Meyer assessment motor component (UE‐FM) within 7 days of stroke and at 15, 30, and 90 days. MRI with tractography was performed within 7 days of stroke. Diffusion tensor images (DTI) were processed to produce maps of fractional anisotropy (FA), apparent diffusion, axial, radial, and mean diffusivity. FA maps were used to assess CST asymmetry index (CST‐AI). Fisher's exact tests for categorical variables, two‐sample t ‐tests for normally distributed numerical data, and Wilcoxon rank sums for non‐normally distributed numeric data were used. Results A total of 21 patients were enrolled in the study with a mean age of 66 (±14) years and median baseline upper extremity motor component score (UE‐FM) of 42 (median) [range: 23, 53]. Baseline UE‐FM was not predictive of a 10‐point change at 90 days ( p = 0.4469). CST‐AI was predictive of recovery at 15 days ( p = 0.0373), and axial diffusivity was predictive of recovery at 90 days ( p = 0.0402). All other imaging variables did not predict recovery. Conclusion Our data suggest that upper extremity motor recovery after acute ischemic stroke is impacted by CST integrity. Further studies are needed to validate our findings.

Introduction: Accreditation of vascular laboratories has been shown to lead to overall improvements in quality patient care. However, there are still factors that needlessly delay the granting of full accreditation. We performed a retrospective analysis looking at factors associated with delays in accreditation in extracranial carotid artery ultrasound examinations by the Intersocietal Accreditation Commission - Vascular Testing (IAC-VT) division. Materials and Methods: We accessed an active database from the IAC-VT division between 2014 and 2020 and extracted data linked to vascular laboratory accreditation in extracranial carotid ultrasound studies. We used the ‘Delay” versus the “Grant” status as outcome and looked at the association with 18 metrics that are part of the application evaluation. We further used a modified Delphi method to determine the relative role played by either the technologist/sonographer or the interpreting physician for each metric. Statistical significance was evaluated by Chi-square. Results: A “Delay” status was assigned in 1638 (58.6%) out of 2794. Ten factors were noted to be significant univariate predictors of a “Delay” status. The three major factors were solely associated with the interpreting physician while adherence to technical factors showed mostly shared responsibility. Conclusion: This retrospective study indicated that the accreditation process is strongly dependent on interpreting physician performance. Targeted interventions may help decrease time and effort associated with the costs of the accreditation process.

OBJECTIVE In phototherapy for neonatal hyperbilirubinemia, the use of covers placed between the newborn and the phototherapy source is variable. Guidelines often recommend a cover for the phototherapy blanket pad. Because covers could affect illumination levels, we assessed phototherapy irradiance levels from an overhead phototherapy system and a phototherapy blanket, with and without commercial covers. METHODS In this nonclinical study, the overhead phototherapy system used calibrated radiometer measurements from 420 to 500 nm at 2 distances below the light source; the phototherapy blanket used measurements from 400 to 520 nm. We measured irradiance in 4 different variations using 2 types of covers (a mesh swaddle and a phototherapy blanket pad). RESULTS For the overhead system, at 30.5 cm below the light source and with a mesh swaddle covering the meter, the irradiance was 29.5 μW/cm2/nm, which was 14% lower than the value without covering (34.4 μW/cm2/nm). The mean irradiance at 15 cm from the light source with the mesh covering the meter (38.5 μW/cm2/nm) was 15% lower than without a cover (45.4 μW/cm2/nm). The irradiance under the zipper of the mesh swaddle was substantially lower at either distance. For the phototherapy blanket, the irradiance measured in all the posterior covering variations ranged from 61.1 (nest plus swaddle) to 98.5 μW/cm2/nm (no covering). CONCLUSIONS Clinicians should be aware that commercial phototherapy coverings affect irradiance; however, optimal irradiance can be achieved and may even exceed current American Academy of Pediatrics (AAP) recommendations of 25 to 35 μW/cm2/nm.

PURPOSE Recent studies reveal that 5%-18% of children with cancer harbor pathogenic variants in known cancer-predisposing genes. However, DNA damage repair (DDR) genes, which are frequently somatically altered in pediatric tumors, have not been systematically examined as a source of novel cancer-predisposing signals. METHODS To address this gap, we interrogated 189 DDR genes for presence of germline predisposing variants (PV) among 5,993 childhood cancer cases and 14,477 adult noncancer controls (discovery cohort). PV were determined using a tiered approach incorporating ClinVar annotations, InterVar classification, and in silico tools (REVEL, CADD, and MetaSVM). Using logistic and firth regression, we identified genes with PV statistically enriched in the germline of children with tumors and replicated findings among 1,497 additional childhood cancer cases across three independent cohorts. RESULTS Analysis across all cases with cancer revealed enrichment of TP53 PV. Cancer-specific analyses confirmed known associations including germline TP53 PV in adrenocortical carcinoma, high-grade glioma (HGG), and medulloblastoma (MB), PMS2 in HGG and non-Hodgkin lymphoma (NHL), MLH1 in HGG, BRCA2 in NHL, and BARD1 in neuroblastoma. In addition, four novel associations were uncovered, including BRCA1 in ependymoma, SPIDR in HGG, SMC5 in MB, and SMARCAL1 in osteosarcoma (OS). Importantly, the SMARCAL1 :OS association was significant in the discovery (6/230, 2.6%, false discovery rate [FDR] logistic = 0.0189) as well as all three replication cohorts (Childhood Cancer Survivor Study: 8/275, 2.9%; P Fisher < .0001; Cancer Predisposition Syndrome-German Childhood Cancer Registry: 4/135, 3%, P Fisher = .002; Individualized Therapy for Relapsed Malignancies in Childhood: 4/217, 1.8%, P Fisher = .012). The remaining wild-type SMARCAL1 allele was deleted in three of four OS tumors with available data. CONCLUSION Our study confirms the relevance DDR genetic variation in pediatric cancer risk and establishes SMARCAL1 as a novel OS predisposing gene, providing insights into tumor biology and creating opportunities to optimize care for patients with this challenging tumor.

Syndrome of the Trephined (SoT), also known as sunken or sinking skin flap syndrome (SSFS), is a rare sequela of decompressive craniectomy caused by an atmospheric pressure gradient over the underlying brain parenchyma following bone flap removal. Cranioplasty is the definitive treatment of SoT, although some patients are not surgical candidates or require bridging to definitive treatment. This systematic review identified 7 articles describing nonsurgical interventions for patients with SoT. Three treatment modalities emerged: external orthotics, scalp traction, and Trendelenburg positioning. These approaches demonstrated rapid improvements in neurological symptoms, including restored motor function, improved cognition, resolution of midline shifts, and, in some cases, re-expanded brain parenchyma. While these results are limited to case reports and small case series, they demonstrate promising early outcomes for the noninvasive management of Syndrome of the Trephined.

Background: Tumor-associated macrophages (TAMs) are essential regulators of the glioblastoma (GBM) microenvironment; their functional heterogeneity and interaction networks are not fully elucidated. We identify RNF135 as a novel TAM-enriched gene associated with immune activation and adverse prognosis in GBM. Methods: To evaluate RNF135’s expression profile, prognostic significance, and functional pathways, extensive transcriptome analyses from TCGA and CGGA cohorts were conducted. The immunological landscape and cellular origin of RNF135 were outlined using single-cell RNA-seq analyses and bulk RNA-seq immune deconvolution (MCP-counter, xCell and ssGSEA). Cell–cell communication networks between tumor cells and RNF135-positive and -negative tumor-associated macrophage subsets were mapped using CellChat. Results: RNF135 predicted a poor overall survival and was markedly upregulated in GBM tissues. Functional enrichment analyses showed that increased cytokine signaling, interferon response, and innate immune activation were characteristics of RNF135-high samples. Immune infiltration profiling showed a strong correlation between the abundance of T cells and macrophages and RNF135 expression. According to the single-cell analyses, RNF135 was primarily expressed in TAMs, specifically in proliferation, phagocytic, and transitional subtypes. RNF135-positive TAMs demonstrated significantly improved intercellular communication with aggressive tumor subtypes in comparison to RNF135-negative TAMs. This was facilitated by upregulated signaling pathways such as MHC-II, CD39, ApoE, and most notably, the CCL signaling axis. The CCL3/CCL3L3–CCR1 ligand–receptor pair was identified as a major mechanistic driver of TAM–TAM crosstalk. High RNF135 expression was also linked to greater sensitivity to Selumetinib, a selective MEK1/2 inhibitor that targets the MAPK/ERK pathway, according to drug sensitivity analysis. Conclusions: RNF135 defines a TAM phenotype in GBM that is both immunologically active and immunosuppressive. This phenotype promotes inflammatory signaling and communication between cells in the tumor microenvironment. Targeting the CCL–CCR1 axis or combining RNF135-guided immunomodulation with certain inhibitors could be a promising therapeutic strategies for GBM.

IDH1/2 mutations (IDH mut ) increase methylation of DNA and histones in gliomas. IDH mut inhibitors are effective against low-grade IDH mut gliomas, but new strategies against high-grade IDH mut gliomas are needed. Although histone deacetylase inhibitors (HDACi) are ineffective against IDH wt glioblastoma (GBM), their potential in IDH mut gliomas has not been extensively studied. We previously established that IDH mut gliomas are more sensitive to HDACi than IDH wt GBM. Here we show that IDH mut is associated with greater sensitivity to HDACi only in glioma, not in IDH mut chondrosarcoma or cholangiocarcinoma. While HDACi induced more histone acetylation and gene regulation in IDH mut glioma than in IDH wt GBM, such acetylation was mostly within gene deserts, whereas IDH mut glioma promoters paradoxically lost histone acetylation. Two mediators of HDACi resistance, YAP and TAZ, were methylated and suppressed in IDH mut gliomas but not in other IDH mut cancers. Inducing YAP or TAZ expression in IDH mut gliomas conferred resistance to HDACi. Finally, belinostat extended in vivo survival only in IDH mut glioma models, not in IDH mut GBM models. Our findings provide a mechanistic rationale for further studies of HDACi in patients with IDH mut glioma, as well as the potential use of YAP/TAZ as a biomarker of HDACi sensitivity in cancers.